Pathogenesis of the Dengue Virus
Our research focuses on the immunology and pathogenesis of dengue virus (DEN), which causes dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), the most prevalent mosquito-borne viral diseases in humans worldwide, with an estimated 2.5 billion people at risk for infection. DEN is a positive-sense, single-stranded RNA virus that belongs to the family Flaviviridae and the genus Flavivirus, which includes yellow fever (YFV), West Nile (WNV), Japanese encephalitis (JEV), and St. Louis encephalitis (SLEV) viruses. Primary infection with any one of the four DEN serotypes typically leads to DF, a debilitating but self-limited acute febrile illness. However, some primary infections and a larger percentage of secondary infections with a different serotype result in the severe, life-threatening DHF/DSS, characterized by increased vascular permeability, thrombocytopenia, and hemorrhagic manifestations. DEN is transmitted to humans by the mosquitoes Aedes aegypti and Ae. albopictus. Due to uncontrolled urbanization, globalization, and the spread of the DEN-transmitting mosquitoes, multiple DEN serotypes co-circulate, resulting in an increase in the frequency of epidemics and in the introduction and spread of DHF/DSS. As a result, dengue is a major public health problem throughout the world. Both Aedes aegypti and Ae. albopictus are now endemic from Georgia through Texas, and the CDC has classified DEN as an emerging disease threat in the United States. At present, DEN-specific therapies and vaccines are unavailable, and the NIAID has listed DEN as a bio-defense category A pathogen.
Despite the global morbidity and mortality, DEN pathogenesis is not yet fully understood. Epidemiologic and in vitro data suggest that DHF/DSS may be an immunopathogenic disease; however, the precise role of the immune system in response to DEN infection in vivo is as yet to be elucidated, mainly due to the lack of an adequate animal model. Therefore, a major goal in our laboratory is to determine the immune and pathogenic mechanisms of DEN infection in vivo. To achieve this goal, we are currently working on the following two projects:
- 1. Identification of immune mechanisms that control DEN infection in vivo.
- 2. Creation of a murine model that resembles DEN disease in humans.